Apparatus for collecting and detecting an analyte in a fluid sample

ABSTRACT

The present invention provides an apparatus for detecting an analyte in a fluid sample, comprising a fluid sample collection element, comprising a fluid sample collection element that comprises an absorbing element; a carrier for accommodating a testing element; and a chamber for accommodating a testing element carrier, wherein the testing element carrier is located in the chamber, and the carrier further comprises an extrusion structure that is in contact with the absorbing element and extrudes the absorbing element.

RELATED APPLICATIONS

This application claims priority to Chinese Patent Application No.201820648661.9, filed on May 3, 2018, which is herein incorporated byreference in its entirety.

FIELD OF THE INVENTION

The present invention relates to an apparatus and a method for detectingan analyte in a fluid sample, and in particular, to an apparatus andmethod for collecting saliva and detecting an analyte in a salivasample.

BACKGROUND

The following background art is provided to assist readers inunderstanding the present invention rather than a prior art.

At present, illegal drug abuse has become a recognized and increasinglyworsening social problem. In 2003, the survey conducted by the USDepartment of Health and Human Services revealed that about 19.5 millionAmericans or 8.2% of people over the age of 12 are taking illegal drugs.“Recent use of illegal drugs” refers to the use of an illegal drugwithin one month before the US Department of Health and Human Servicesconducted a survey. Cannabis is found to be the most commonly usedillegal drugs, accounting for 6.2% (14.6 million). Now about 2.30million people (1.0%) are using cocaine, 604,000 people use Crack, and 1million people are using hallucinogens, and it is estimated that 119,000people are using heroin.

In order to fight against the drug abuse and monitor this socialproblem, the drug testing has become a standard test procedure invarious industries such as hiring, education, sports, and lawenforcement, etc. To promote this standard testing procedure, the drugtesting industry has formed. This industry has provided a wide range ofdrug testing products. The urine sample collection cup for sampleanalysis is a classic testing product. These devices may be complex,difficult or dirty for users, or may cause the problem of adulterationin the sample to conceal the use of illegal drugs recently. In additionthe urine samples cannot be collected in some cases, for example, on theroadside or in the public places.

Various sample collection and testing apparatuses for clinical ordomestic use are available and described in some literatures. Forexample, the U.S. Pat. No. 5,376,337 disclosed a saliva samplingapparatus in which in which a piece of filter paper is used to collectsaliva from examinee's mouth and deliver saliva to an indicator reagent.The U.S. Pat. Nos. 5,576,009 and 5,352,410 disclosed a syringe-typefluid sampling apparatus respectively. For these apparatuses, after theinitial results are obtained, fluid samples collected cannot be storedfor subsequent confirmatory testing. Further, for another example, theU.S. Pat. No. 7,927,562 disclosed a saliva collection apparatus, butthere are still some drawbacks, for example, when the saliva samplescollected by the absorption portion are not enough, the squeezing andreleasing is still insufficient, resulting in insufficient samples andfailure to complete the testing; or sometimes there are too much liquidpartially, causing flooding and unable to obtain correct detectionresults.

Many other sample collection and testing apparatuses are inefficient inextracting samples from the collection apparatus. Many of theseapparatuses are very complex in the design and manufacturing, requiringexpensive materials. Therefore, it is necessary to collect and testsamples with better method and apparatus.

SUMMARY

In order to solve the existing problems in the prior art, the presentinvention provides an apparatus for collecting and detecting an analytein a fluid sample, comprising: a fluid sample collection element thatcomprises an absorbing element; a testing element carrier; and a chamberfor accommodating a testing element carrier, wherein the testing elementcarrier is located in the chamber.

In some preferred embodiments, the apparatus further comprises anextrusion structure for extruding the absorbing element. In somepreferred embodiments, the extrusion structure and the testing elementcarrier are an integrated structure, or the extrusion structure islocated on a testing element carrier. In some preferred embodiments, theextrusion structure cooperates with the absorbing element to compressthe absorbing element. In some preferred embodiments, the contact of theextrusion structure with the absorbing element is accomplished by thecooperation of the collection element with the opening of the chamber.

In some preferred embodiments, the extrusion structure comprises areceiving chamber corresponding to the absorbing element, and thereceiving chamber is used to receive or carry the absorbing element. Insome preferred embodiments, the carrier comprises an inner surface andan outer surface, the outer surface being provided with one or moregroove structures, and the groove structure is provided with a testingelement. The testing element is a lateral flow test strip. The outersurface of the carrier and the inner surface of the chamber thataccommodates the testing element carrier form a separate chamber. Insome embodiments, the extrusion structure is located at the bottom ofthe carrier. In some embodiments, the position of the extrusionstructure is higher than the bottom of the chamber that accommodates thetesting element carrier. In some embodiments, the testing elementcarrier comprises a support structure that is located at the bottom ofthe chamber. In some preferred embodiments, a collection area is formedat the bottom of the chamber that accommodates the testing elementcarrier, to collect liquid samples that are extruded by the extrusionstructure from the carrier.

In some preferred embodiments, the fluid sample collection elementcomprises an absorbing element for collecting liquid samples and agripping portion. In preferred embodiments, the gripping portion has astructure that cooperates with an opening of the chamber thataccommodates the testing element carrier, by this way, when the fluidsample collection element is inserted into the chamber that accommodatesthe testing element carrier, the gripping portion cooperates with theopening of the chamber that accommodates the testing element carrier, sothat the fluid sample collection element is “retained” in the chamberthat accommodates the testing element carrier. In some preferredembodiments, the gripping portion has a matching structure with theopening of the chamber that accommodates the testing element carrier, sothat the collection element can be retained in the chamber. In preferredembodiments, the gripping portion has a structure matching with theretaining element such that the fluid sample collection element isretained in a relatively fixed position in the chamber that accommodatesthe testing element carrier.

In some preferred embodiments, the gripping portion comprises a flexibleannular structure that cooperates with the opening of the chamber toseal the opening of the chamber. In some embodiments, the apparatuscomprises an inner plug that is connected with the gripping portion. Aflexible sheet-like structure is disposed on the inner plug. Here, the“inner plug” refers to the part for entering the chamber or part of theinner plug enters the chamber. Therefore, a flexible sheet-likestructure is provided on the inner plug to facilitate sealing of theopening of the chamber; in addition, as the inner plug is connected tothe collection element, the collection element can retain the chamber;here the chamber refers to the chamber for accommodating the carrier. Insome preferred embodiments, the flexible annular structure is amulti-layer structure, each layer of structure has the property offlexibility. When the absorbing element is inserted into the chamber,the sealing ring cooperates with the opening of the chamber to from aseal. In some preferred embodiments, the flexible annular structure alsoserves to maintain the collection element in the chamber. The ring is asheet-like structure that surrounds the gripping portion or the innerplug. The outer diameter of the sealing ring is larger than the innerdiameter of the opening of the chamber, so that the sealing ring isdeformed to form a sealing structure and retain the collection elementin the chamber when the sealing ring is in contact with the inner wallof the opening of the chamber. In some preferred embodiments, thesealing ring is flexible and in the form of a sheet, with a triangularcross-sectional shape. When contacting the inner wall of the chamber,the triangular side is in contact with the inner wall to form a seal,and at the same time, the collection element is retained in the chamber.In some preferred embodiments, the sheet structure has a plurality oflayers, or at least 2 layers, or at least 3 layers, at least 4 layers,at least 5 layers. The more the number of layers of flexible sheetstructure, the better the sealing effect, and the better the stabilityof the collection element fixedly retained in the chamber.

Preferably, the gripping portion cooperates with the chamber thataccommodates the testing element carrier in a way of locking, fastening,plugging or buckling, so that the fluid sample collection element isretained in the chamber that accommodates the testing element carrierwhen inserted, or the fluid sample collection element is in a relativelyfixed position. The “retain” herein means that the collection element isinserted into the chamber that accommodates the testing element carrierafter collecting samples, and under one of the states, the collectionelement is in a relatively fixed position in the chamber thataccommodates the testing element carrier and cannot be inserted anylonger.

In some preferred embodiments, the absorbing element is connected to thegripping portion via a rod. Preferably, the collection element, gripingportion and connecting rod is an integrated structure.

In some preferred embodiments, the body accommodating the testingelement and the chamber for receiving the absorbing element are anintegrated structure. The integrated structure can be formed by one-shotinjection molding, or can be formed by the body accommodating thetesting element and the chamber for receiving the absorbing elementthrough bonding by a laser or a bonding agent.

In some preferred embodiments, the chamber that accommodates the testingelement carrier is roughly a structure with elliptical or circularcross-section. The chamber receives the carrier. The other surfaces ofthe chamber that accommodates the testing element carrier can betransparent or not transparent.

In another aspect, the present invention provides an apparatus forcollecting and detecting an analyte in a fluid sample, comprising:

a fluid sample collection element, wherein the fluid sample collectionelement comprises an absorbing element that absorbs fluid samples and agripping portion, and a connecting rod that connects the absorbingelement and the gripping portion;

a testing element carrier, wherein the testing element carrier comprisesa body for carrying a testing element and an extrusion structure forcontacting the absorbing element and extruding the absorbing element;

a chamber for accommodating a testing element carrier;

wherein, the gripping portion further comprises a flexible sealing sheetstructure, and the sealing sheet structure cooperates with the innerwall of the opening of the chamber that accommodates the testing elementcarrier, thereby forming an opening for sealing the chamber, andallowing the sample connection element to be retained in the chamberthat accommodates the testing element carrier.

In still another aspect, the present invention provides a collectionapparatus, comprising an absorbing element that absorbs liquid samples,and a gripping portion. The absorbing element is connected to thegripping portion by a connecting rod, wherein the apparatus furthercomprises an inner plug body, and one layer or multiple layers offlexible sheet-like structures are provided on the inner plug body.

In some other preferred embodiments, the flexible sheet-like structurehas different outer diameter.

In some other preferred embodiments, the flexible sheet-like structurehas an acute triangle section.

In some other preferred embodiments, for the two long sides of the acutetriangle, one side is perpendicular to the inner plug body 108, and theother side is inclined with the inner plug body.

In some other preferred embodiments, the long side perpendicular to theinner plug is located above the long side inclined with the inner plugbody.

In some other preferred embodiments, the outer diameter formed by theinner plug and the flexible sheet-like structure is smaller than theouter diameter of the inner portion.

Beneficial Effect

The apparatus of the present invention can achieve convenient and quickdetection and reading of results; in addition, with low production cost,the detection apparatus is more accurate, without causing flooding.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic exploded perspective view of a collection anddetection apparatus according to an embodiment of the present invention.

FIG. 2 is a perspective structural view of a carrier for accommodating atesting element according to an embodiment of the present invention.

FIG. 3 is a top view of the testing element carrier in FIG. 2 .

FIG. 4 is a schematic longitudinal sectional view of a chamber thataccommodates a testing element carrier.

FIG. 5 is an assembled structural view of a carrier and a chamberaccommodating a testing element according to an embodiment of thepresent invention.

FIG. 6 is a schematic perspective view of a gripping portion of acollection element.

FIG. 7 is a schematic longitudinal sectional view of a gripping portionof a collection element.

FIG. 8 is a schematic diagram showing the combined structure of theapparatus shown in FIG. 1 according to an embodiment of the presentinvention, showing the structure of extruded state of the absorbingelement.

FIG. 9 is a schematic diagram showing defects in saliva extrusion anddetection in comparison with conventional techniques.

DETAILED DESCRIPTION

The structures involved in this invention or the used technical termsare further described below. These descriptions are only to explain howto achieve the ways in this invention through examples, and will notrestrict this invention.

Detection

Detection means to assay or test the presence or absence of a substanceor material, including but not limited to chemical substances, organiccompounds, inorganic compounds, metabolic products, medicines or drugmetabolites, organic tissues or metabolites of organic tissues, nucleicacids, proteins or polymers. Additionally, detection means to test thequantity of a substance or material. Furthermore, assay also meansimmunodetection, chemical detection, enzyme detection, and etc.

Testing Element

Various testing elements can be combined and applied to this invention.The testing element comprises a test strip, which can be analyzed invarious forms such as immunoassay or chemical test to detect suchanalyte in samples as drugs or relevant metabolites indicating physicalconditions. In some forms, the test strip is a water absorbent materialhaving sample applying area, reagent area and testing result area.Samples are added to the adding area, and flow to the reagent area underthe capillary action. In the reagent area, samples dissolve the reagentand mix with it to detect analyte (if there is analyte in samples). Atthis time, samples with reagents continue to flow to the testing resultarea. Other reagents are fixed in the testing result area, and thesereagents react and combine with analyte (if there is analyte in samples)or the first type of reagent in the reagent area. In the noncompetitivedetection form, if there is analyte in samples, signals will begenerated; and if not, signals will not be generated. In the competitivedetection form, if there is no analyte in samples, signals will begenerated; and if not, signals will not be generated. The inventionapplies to the testing element of various analytic forms.

When the testing element is a test strip, it can be made from waterabsorbent or non-water absorbent materials. A test strip can use variousmaterials to transmit liquid, and one material can be superposed onanother material. For example, a filter paper can be superposed on thenitrocellulose. Or in the test strip, a region that at least containsone material is located behind the other region that at least contains adifferent material. In such case, the liquid circulates among regions,and they can be superposed on one another or choose not to superpose.Materials on the test strip can be fixed on (for example) the holder orhard surface of the plastic gasket, to enhance the test strip'ssustainable power.

In some embodiments where some detected objects are detected through asignal generation system (for example, at least one enzyme reactsspecifically with the detected object), at least one substancegenerating signals can be absorbed on the analyte detecting area of thetest strip, just like being absorbed specifically on the materials ofthe test strip as described above. In addition, substances generatingsignals in the sample adding area, reagent area and analyte detectingarea of the test strip or all over the whole test strip can bepretreated in advance on one or more materials of the test strip, whichcan be achieved by adding the solution of substances generating signalsto the surface of the application area or soaking one or more materialsof the test strip in the signal solution, after which dry the teststrip. Moreover, the above method can be used to pretreat substancesgenerating signals in the sample adding area, reagent area and analytedetecting area of the test strip or all over the whole test strip inadvance on one or more materials of the test strip. Furthermore, thesignal substance existing in the sample adding area, reagent area anddetecting area of the test strip can be added to one or more surfaces ofthe test strip materials as the labeling reagent.

Areas of the test strip can be arranged as follows: a sample addingarea, at least a reagent area, at least a testing result area, at leasta control area, at least an adulteration detecting area and a liquidabsorption area. If the detecting area comprises a control area, thepreferred control area is located behind the analyte detecting area ofthe testing result area. All these areas or their combinations can be ona single test strip containing a material. Additionally, these areas aremade from different materials, and are connected together according tothe transmission direction of liquid. For example, liquid can betransmitted directly or indirectly among different areas. In thisembodiment, different areas can be connected end to end or superposedmutually along the direction of liquid transmission, or connectedthrough other materials such as connecting medium materials (waterabsorbent materials such as filter paper, glass fiber or nitrocelluloseare preferred). By use of the connecting materials, the liquid can flowon materials that connect each area end to end, materials that connecteach area end to end but the liquid does not flow, or materials thateach area is overlapped mutually (including but not limited tooverlapping from end to end) but the liquid does not flow.

If the test strip contains an adulteration detecting control area, thearea can be arranged before or after the result detecting area. When theresult detecting area contains a control area, the adulteration controlarea is preferred to be arranged before the control area. In oneembodiment of this invention, the test strip is used for analyticaljudgment and/or control of adulteration. The adulteration control areacan be arranged before or after the control area, and preferably, beforethe control area.

In a specific embodiment of the invention, the testing element or teststrip may be located in the testing element carrier 200. Preferably, itis located in the slot 201 of the body of the testing element carrier.In some preferred embodiments, the carrier has two surfaces: an innersurface 208 and an outer surface 205, and the slot 201 is disposed onthe outer surface 205. The length of the slot is equivalent to thelength of the test strip, so that the sample applying area of the teststrip is exposed to the carrier, or partially exposed, by this way, aportion of the sample applying area can be located in the groove 302 atthe bottom of the chamber to contact the liquid samples. In someembodiments, there is a plurality of slots on the surface, for example,1-20 slots, and the analytes detected by the test strips disposed ineach slot are different.

Samples

The detection apparatus provided in the invention can be used to detectsamples including biological liquid (such as case liquid or clinicalsamples). The liquid sample or fluid sample can come from solid orsemi-solid samples, including excreta, biological tissues and foodsamples, and these solid or semi-solid samples can be converted toliquid samples by using any suitable methods such as mixing, crushing,macerating, incubating, dissolving or digesting the solid samples in asuitable solution (such as water, phosphate solution or other buffersolutions) with the enzymolysis. “Biological samples” comprise samplesfrom animals, plants and food, such as urine, saliva, blood and itscomponents, spinal fluids, vaginal secretion, sperms, excrement, sweat,secreta, tissues, organs, tumors, cultures of tissues and organs, cellcultures and media from human or animals. The preferred biologicalsample is urine; food samples comprise food processed substances, finalproducts, meat, cheese, liquor, milk and drinking water; and plantsamples comprise samples from any plants, plant tissues, plant cellcultures and media. “Environmental samples” come from the environment(such as liquid samples coming from lake or other water bodies, sewagesamples, soil samples, underground water, sea water and effluentsamples), and can also comprise waste water or other sewage water.

Any analyte can be detected by using this invention and a suitabletesting element. Preferably, this invention is used to detect thenarcotics in the saliva.

Analyte

Examples that can use the analyte related to this invention include somehapten substances, including drugs (such as drug abuse). “Drug abuse”(DOA) means to use drugs (often to paralyze the nerves) for non-medicalpurposes, which will lead to physical and mental damages, and people whouse drugs will be dependent on, addicted to drugs and/or die. Examplesof drug abuse include abuse of cocaine, amphetamine AMP (e.g. BlackBeauty, white amphetamine tablets, dextroamphetamine, dextroamphetaminetablets, Beans); methylamphetamine MET (crank, meth, crystal, speed);barbiturate BAR (such as Valium, Roche Pharmaceuticals, Nutley, N.J.);sedatives (i.e. sleeping adjuvants); lysergic acid diethylamide (LSD);inhibitors (downers, goofballs, barbs, blue devils, yellow jackets,methaqualone); tricyclic antidepressants (TCA, i.e. imipramine,amitriptyline and doxepin); methylene dioxymetham-phetamine MDMA;phencyclidine (PCP); tetrahydrocannabinol (THC, pot, dope, hash, weedand etc.); opiates (i.e. morphine MOP or opium, cocaine COC, heroin,OXY); antianxiety drugs and sedative hypnotics, the antianxiety drugsare drugs mainly used to relieve anxiety, tension, fear and stabilizeemotions, having the function of hypnosis and sedation, including BZO(benzodiazepines), atypical BZ, fused dinitrogen NB23C, benzodiazepines,ligand of BZ receptors, open-loop BZ, diphenylmethane derivatives,piperazine carboxylate, piperidine carboxylate, quinazolinones,thiazines and thiazole derivatives, other heterocyclic, imidazolesedatives/painkillers (such as OXY, MTD), propanediolderivatives-carbamates, aliphatic compounds, anthracene derivatives andetc. The detection apparatus provided in this invention can also be usedto detect medicines that are easy to overdose for the medical purpose,such as tricyclic antidepressants (imipramine or analogues) andacetaminophen. These medicines will be resolved into differentmicromolecular substances after being absorbed by human body, and thesemicromolecular substances will exist in blood, urine, saliva, sweat andother body fluids or in some of the body fluids.

The analyte detected by this invention includes but not limited tocreatinine, bilirubin, nitrite, (non-specific) proteins, holinones (suchas human chorionic gonadotropin, progesterone hormone,follicle-stimulating hormone), blood, leucocytes, sugar, heavy metals ortoxins, bacterial substances (such as proteins or sugar substancesagainst specific bacteria, such as Escherichia coli 0157:H7,staphylococcus, salmonella, fusobacterium, campylobacter, L.monocytogenes, vibrio or Bacillus cereus) and substances relevant withthe physiological features in the urine sample, such as pH and specificgravity. For any other clinical urine chemical analysis, the detectioncan be made by combining the lateral cross flow detection form and theapparatus provided in this invention.

Sample Collection Element

The present invention further provides a fluid sample collectionelement. In one embodiment, the fluid or liquid sample collectionelement comprises an absorbing element 503 and a gripping portion 100.The absorbing element 503 is generally made of a medical grade sponge orfoam material commonly used in the art. However, the absorbing elementcan also be made of many other materials, such as cotton or paper, orany other material having water absorbing property. The gripping portion101 is generally rigid, which can facilitate the operation of theabsorbing element. The gripping portion 101 can be made of materialscommonly used in the art, such as plastic, wood, metal or cardboard. Inone embodiment, the gripping portion is connected to the absorbingelement 503 through a rod structure 502, and one end of the rodstructure is connected to the griping portion 101, and the other endincluding a wheel edge (see the FIG. 1 attached) and an absorbingelement 503 are attached thereto. In some specific embodiments, thewheel edge comprises a sealing element, for example, a siliconeelastomeric sealing ring (which may or may not be included), for sealingthe absorbing element 503 into the receiving chamber 404 formed by theextrusion structure 400 of the carrier 200. In some embodiments, thegripping portion 100 comprises a holding portion 101 and a flexiblesheet structure 102. The holding portion is used for collecting samplewhere the hand is held. By this way, the absorbing element 503 isconveniently placed in the mouth to collect the saliva sample. Thus, thevolume of the holding portion is relatively large, facilitating to beheld by hands without falling off. For example, as shown in FIG. 6 andFIG. 7 , an annular elastic sheet 102 is provided on the extension ofthe holding portion 101. These loop and wing-like structures areflexible, when the holding portion with the absorbing element isinserted to the chamber 300, the elastic sheet structure 102 cooperateswith the inner wall 303 of the chamber opening. Generally, the innerwall of the chamber opening is smooth without a threaded structure. Theflexible sheet-like structure 102 cooperates with the inner wall, toform an opening-sealed state (FIG. 8 ). Since the flexible structure isin contact with the inner wall, the flexible structure deforms, such asflipping up, to achieve more close contact with the interior, therebyallowing the collection element to be retained in the chamber 300 andnot easily detached from the chamber. In the following text, theadvantages and effects of the flexible structure are described indetails with the extrusion process of the absorbing element.

In some preferred embodiments, the gripping portion is connected to aninner plug or an inner plug is disposed on the gripping portion, whilethe flexible sheet-like structure is disposed on the inner plug, by thisway, when the inner plug is inserted into the inner wall of the openingof the chamber 200, the flexible sheet structure is in contact with theinner wall, playing a role of sealing, in addition, retaining theabsorbing element in the chamber or the extrusion chamber on thecarrier. Actually, the process when the inner plug is inserted into theopening of the chamber 200 is the process in which the absorbing elementis squeezed to release the collected liquid samples.

In order to better secure or bond the holding portion with the absorbingelement to the inner wall 303 of the opening of the chamber 200, theflexible sheet structure may be a multi-layer structure, for example, asshown in FIG. 7 , a five-layer structure. Of course, optionally, themaximum outer diameter of the flexible sheet-like structure is slightlylarger than the diameter or inner diameter of the inner wall 303 of thechamber 200, by this way, when a flexible sheet-like structure with awing shape is inserted into the inner wall of the chamber opening, theflexible structure has an upward flip, while the wing-shaped structurehas a larger area to contact with the inner wall, so that it can form aseal, to allow the absorbing element to retain in the chamber 303.Therefore, in some embodiments, the sheet-like structure 103 canencircle the entire inner plug body 108, wrapping the flexiblesheet-like structure 103 outwardly on the body. In some embodiments, thesheet-like structure has a triangular cross section, and the triangle isan acute triangle. Two sides 104 and 105 constitute the acute triangle,of which one side 104 is substantially vertical to the inner plug body108, while the other side is inclined to the inner plug body. Thus, whenthe inner plug body is inserted into the chamber 300, the apex of thetriangle is in contact with the inner wall, and as the insertioncontinues, part of the sheet-like structure is turned outwardly, so thatthe oblique side 105 is upward, and the longer oblique side 105 is incontact with the interior 303 of the chamber to form a sealed structure.Because the contact has a great friction, the absorbing element isretained in the chamber 303, forming a fixed structure.

In order to connect the absorbing element 503 with the griping portion100, a threaded structure is provided in the inner plug body 108. Theconnecting rod 502 has a thread at one end and an absorbing element atthe other end, thereby connected to the gripping portion in a threadway.

Testing Element Carrier

The carrier of the testing element of the present invention is thecarrier 200 primarily used for carrying the testing element, comprisinga body that accommodates the testing element. The body includes twosurfaces: inner surface 208 and outer surface 205. A plurality of slots201 are provided on the outer surface 205 of the body, and a testingelement can be disposed or placed in the slot 201. In order to allow thetesting element to be fixedly placed in the card slot 201 withoutdetaching, two pairs of protrusions 2 are provided in the card slot 201,to maintain the testing element and prevent from detaching from the slot201. In some embodiments, the sample absorption area of the testingelement is exposed out of the body and extended from a section ofopening 202 of the card slot 201, to directly contact with the fluidsamples. In one embodiment, the exposed portion of the testing elementis located in the collection area 302 of the chamber 300, to contact theliquid samples and form a liquid communication state.

In some embodiments, when the testing element is disposed in the slot201, the surface 201 is covered with a transparent sheet, such asplastic, aluminum foil, adhesive sticker, etc., allowing the test stripin a dry environment or not to be affected by the external environment,for example, avoid accidental damage to the test strips during theassembly process. Of course, the sample absorption area of the teststrip may not expose the opening of the card slot. Optionally, the outersurface of the carrier does not have any sheet covering the groove, butdirectly matches with the inner wall of the chamber. That is, the shapeof the chamber is mutually adapted to the shape of the carrier, forexample, the chamber is elliptical, then the carrier is also elliptical,such that the outer surface 205 of the carrier is in contact with theinner surface 308 of the chamber 300, allowing the inner surface 308 ofthe chamber to cover the slot 201 of the carrier 200.

Of course, it is also possible to prevent the outer surface 205 of thecarrier from forming a tight fit with the inner surface 308 of thechamber, to facilitate assembly. Generally the carrier is one-slotinjection molding. After completion, the testing element is disposed onthe slot 201 of the outer surface of the carrier, allowing the sampleapplying area to slightly expose the opening 202 and extend out of thecarrier. When the carrier with the testing element is placed in thechamber 300, the sample applying area of the testing element is placedin the collection area 302 at the bottom of the chamber 300 to contactthe liquid samples (as shown in FIG. 5 ).

In some preferred embodiments, a structure for extruding the absorbingelement, such as the structure 400, is also provided at the bottom ofthe carrier. The structure is also adapted to the shape of the carrier.For example, the shape of the carrier is elliptical, then the extrusionstructure is also elliptical. One or more holes 401 are provided in theextrusion structure, and two holes 402 and 403 are also disposed at thejunction of the extrusion structure and the carrier, so that the liquidsamples released by absorbing element and extrusion structure due tocompression will flow to the bottom of the chamber 300 through theseholes, which will be collected in the collection area 302. Thecollection area 302 at the bottom of the chamber is formed by an area301 that protrudes upwardly from the bottom of the chamber.

In some embodiments, the extrusion structure is a recessed chamberstructure, with an extrusion chamber 404 having a plurality of holes 401at the bottom thereof. There are one or more holes in the chamberconnected to the carrier. For example, as shown in FIG. 5 , when theabsorbing element is received by the chamber structure and compressed,the liquid can flow into the chamber 300 that receives the carrierthrough the hole 401 at the bottom of the extrusion chamber 404, or flowinto the chamber 300 that receives the carrier through the hole 402 atthe side surface.

Such a design has a number of advantages over existing conventionalsaliva collection apparatus. For example, as described in the U.S. Pat.No. 7,927,562, a protrusion structure 503 and a collection area 540 areprovided at the bottom of the chamber receiving carrier as shown inFIGS. 1-6 , allowing the absorbing element to contact with theprotrusion structure 503 and squeezing the convex absorbing element torelease the liquid samples. Actually, since the absorbing element 300has a certain length, it usually becomes very soft after absorbingliquid samples, and actually there is a testing element 600 in thecollection area 504, when the protrusion structure 503 is in contactwith the absorbing element 300 absorbing the liquid samples, theabsorbing element is not linearly compressed, but a phenomenon ofbending and folding will occur. Such a bent and folded absorbing elementwill touch the test strip of the accessory or touch the samplingportion, thereby causing an increase in the local liquid amount. Theliquid is not necessarily collected in the collection area 504 butadsorbed by the test strip directly. By this way, excessive liquidsamples exist on some test strips, causing a flooding phenomenon, forexample, as shown in FIG. 9 , the liquid in other test strips will bereduced, thus, some test strips have excessive liquid, while some havevery few liquid and unable to complete reactions, affecting the finaldetection results. In FIG. 9, 60 represents a test strip, and 51represents an absorbing element (softened after absorbing liquid), 50represents a protrusion, which contact with the absorbing element 60 tosqueeze a liquid sample, and 52 represents a chamber. Moreover, theabsorbing element is on the gripping portion 105, and the grippingportion is rotated and engaged with the chamber 506 by the thread, bythis way, the absorption portion will also rotate, actually, it isrotated while compressed, such that the bent and folded absorbingelement will contact with a number of testing elements. Moreover,sometimes the testing element is bent while the liquid is absorbed(becoming soft after absorbing liquid), or, as the absorbing elementrotates, the sample applying areas of adjacent testing elements will beinterleaved together, causing cross-reactions that affect the detectionstructure of the reagents. This is because the analytes corresponding toeach test strip is different. In addition, the “test tube” as describedin U.S. Pat. No. 7,927,562 is circular, which is inconvenient to take apicture or scan after the test.

The present invention overcomes these drawbacks. The structure thatextrudes the absorbing element is moved away from the testing element,so the absorbing element will not touch any part of the testing element.Therefore, in some preferred embodiments, the structure 400 thatextrudes the absorbing element or the extrusion chamber 404 thatreceives the absorbing element is away from the bottom of the chamber300. Therefore, preferably, the carrier has a support structure 209,which surrounds the bottom space of the carrier, such that the bottom ofthe extrusion structure is located within the space 600 enclosed by thesupport structure, or the support structure surrounds the extrusionstructure, as shown in FIG. 5 . The extrusion structure 400 is inwardlyrecessed from the space 600 enclosed by the support structure, so thatthe test strip located in the groove on the carrier surface will notcontact the absorbing element, thereby avoiding the flooding phenomenon.In addition, since the absorbing element 102 with the flexiblesheet-like structure is in contact with the wall of the opening of thechamber 300 and it is a plug-in method without rotating, the absorbingelement will not be rotated, thereby avoiding the contact between theabsorbing element and the test strip or intersection of test strips.

In some specific embodiments of the present invention, the carrier ofthe testing element further comprises an extrusion chamber 404 thatreceive the absorbing element 503, the chamber includes the bottom ofthe chamber having one or more through-holes 401, such as fourthrough-holes arranged symmetrically. The diameter of the through-hole401 may be smaller than the diameter of the absorbing element 503. Whenthe absorbing element contacts the bottom, it may be pressed by theacting force, so that the liquid samples absorbed on the absorbingelement 503 are extruded, thereby flowing out via the through-hole 401.Preferably, the diameter of the through-hole 401 is substantially thesame as the diameter of the absorbing element 503, and a hollow “cross”structure is disposed at the through-hole, by this way, when theabsorbing element contacts the “hollow” structure at the bottomthrough-hole, it can be squeezed by the force, such that the liquidsample absorbed on the absorbing element 103 are extruded to flow intothe bottom of the chamber 300 and collected in the collection area 302.

In some preferred embodiments, the chamber 404 and the carrier 200receiving the testing element carrier are an integrated structure.Preferably, the chamber 4047 and the carrier 200 are one-shot injectionmolded. A card slot 201 is provided on the carrier 200.

Chamber that Accommodates the Testing Element Carrier

In a specific embodiment, the shape of the chamber 300 that accommodatesthe testing element carrier of the present invention is shown as in theFIG. 4 . In addition to such structure, other appropriate structures maybe provided. The chamber 300 that accommodates the testing elementcarrier is enclosed by an opening, a side wall and a bottom. The openingis used to allow the chamber that accommodates the testing elementcarrier 200 to enter the chamber 300. The height of the carrier 200 isless than that of the chamber. A support structure 209 is provided inthe carrier, to form a structure relative to FIG. 5 . A smooth innerwall 303 is provided at the opening. The smooth interior is connectedwith the flexible sheet-like structure 102 of the gripping portion, sothat the flexible sheet-like structure is in contact with the innerwall, which plays a role of sealing and allows the collection elementwith an absorbing element to retain in the chamber. In contrast to thestructure disclosed in U.S. Pat. No. 7,927,562, it is a threadstructure, with thread on the chamber, therefore it increases theprocessing cost. In addition, the thread structure can only play amatching function, which is difficult to seal. When the test iscompleted and there are surplus liquid samples in the chamber, theliquid will leak from the thread joint to contaminate the externalenvironment during the transportation. In the present invention, theflexible sealing sheet is in close contact with the inner wall of thechamber to provide a sealing effect and prevent the liquid in thechamber 300 from leakage. In fact, it is also unlikely that thestructure of the plug is provided here. If the ring-shaped structurewith the flexible sheet is removed and the flexible plug is used, thedrawback is that, when the plug enters the chamber 300, the sealingeffect is formed. However, since the opening of the chamber 300 issealed, the plug is difficult to re-enter into the chamber 300 tocompress the absorbing element 502 once sealed. Due to the sealedenvironment, the sealed gas is in the chamber, so a great force isrequired to allow the plug to enter the chamber 300. In the presentinvention, a multi-layer flexible sheet-like structure is adopted, whichcan form a seal by contacting the inner wall 303 of the smooth chamberalong the edge of the sheet, thereby it is not difficult to form aliquid seal, and at the same time, the collection element with anabsorbing element 503 is combined with the chamber 300 (as shown in FIG.8 ).

In some embodiments, since the carrier 200 also form an inner chamber208 in the chamber 300, the flexible sheet-like structure disposed onthe inner plug body 108 does not have the same outer diameter, which maybe different, for example, a first layer of flexible sheet-likestructure 109 and a second layer and third layer of flexible sheet-likestructure 107 are provided from bottom to top, but the outer diameter ofthe first layer of flexible sheet-like structure 109 is smaller thanthat of the second layer and third layer of flexible sheet-likestructure. By this way, the first layer of flexible sheet-like structure109 and the carrier form an inner wall of the chamber 208, that is,contact with the inner wall of the carrier, so that this part offlexible sheet-like structure is in contact with the inner wall of thechamber 200, and part is in contact with the inner wall 208 of thecarrier, playing a role of double seal and double retention.

Here, the carrier is elliptical, and the chamber 200 is also elliptical.A plurality of grooves for accommodating the test strips is disposed onthe two long sides of the elliptical carrier, when the detection isfinished, the detection results can be obtained by scanning. Theelliptical setting is more convenient for saving the results.

Detection Method

The detection method of analytes in the fluid samples is described inconjunction with the drawings.

A fluid collection element and an assembled detection apparatus areprepared. The detection apparatus comprises a chamber 300 thataccommodates the testing element carrier and is located in a receivingelement carrier 200 (as shown in FIGS. 1-6 ). Wherein, the fluidcollection element comprises an absorbing element 503 that absorbs afluid sample and a gripping portion 100 with a flexible sheet-likestructure 102. The gripping portion 100 comprises a hand-held portion101 and a plurality of ring-shaped flexible sheet-like structures 102 toconnect 503 to the absorbing element through a connecting rod 502,thereby forming a specific fluid collection element. The absorbingelement 503 is placed in the mouth for collecting saliva. When theentire absorption head is filled with saliva samples, the absorptionhead becomes soft. At this time, the collection element that absorbs thesaliva samples is inserted into the chamber 300 that accommodates thetesting element carrier through the opening. With the entering orinserting of the collection element, the liquid absorbing element entersthe receiving cavity 404. At this time, as the flexible sheet layer ofthe inner plug body gradually enters the opening of the chamber 300, itcooperates with the inner wall. By this way, the absorbing element 503is compressed in the extrusion chamber 404, thereby releasing the liquidsamples to flow into the bottom of the chamber through the hole 401, andwith further extrusion, the saliva retained in the absorbing element 103is squeezed out, and the liquid samples released from the bottom of theabsorbing element flow to the protrusion area through the through-hole406, and the saliva samples are collected into the collection groove302, while the liquid samples extruded from the upper portion of theabsorbing element 503 flow through the hole 402 to the protrusion area,the saliva samples are collected into the collection groove 302, tocontact with the absorption area of the testing element in the groove,so that the saliva samples rise along the testing element due tocapillary action and flow to the detecting area, to perform detection ofanalytes.

When the collection element 10 is inserted into the chamber 300 thataccommodates the testing element carrier, a plurality of flexiblesheet-like structures 102 are in contact with the inner wall 303 at theopening of the chamber 300, achieving the sealing of the opening of thechamber 300. In addition, with the insertion, the absorbing element 503is compressed, and the frictional force formed by the close contactbetween the flexible sealing sheet and the inner wall is sufficient toovercome the reaction force of the absorbing element when beingcompressed, thereby allowing the absorbing element and the entirecollection to be retained on the chamber 300. When the detection isfinished, the apparatus can be directly sent to a detection agency forsecond confirmatory detection when necessary. As the sealing of theflexible sealing sheet does not cause liquid leakage, when performingthe secondary detection, the collection element 10 is taken out of thechamber 300 to collect the remaining liquid samples for secondary assay.

Example 1

150 saliva samples are collected from 150 subjects using the samplecollection element described herein by placing the absorbing element 503of the sample collection element in the subject's mouth until filledwith saliva. After samples are collected, the sample collector is placedin the extrusion chamber 404 of the apparatus that accommodates thetesting element carrier 200 to compress the absorbing element 503, andextrude samples and then directly detected. The 50 negative samples aremixed with a mixture of drugs of abuse, including amphetamine, cocaine,methamphetamine, opiates, THC, and phencyclidine. The same proceduresare performed using the absorbing element 503 to collect liquid. 10minutes later, the results are recorded as positive or negative. Threetest strips are placed on each carrier 200, and each test strip can testthree kinds of drugs of abuse. The following six drugs of abuse aredetected by the three test strips: amphetamine (AMP), cocaine (COC),methamphetamine (MET), opiates (OPI), tetra-hydrocannabinol (THC) andphenylcyclohexylpiperidine (PCP).

The 100 samples without drugs of abuse are tested negative, with acompliance rate of 100%. For each of the six drugs, positive results areprovided for 50 samples that have been spiked with the drug mixture,with a compliance rate of 100%.

Similarly, the same test is carried out using the apparatus described inU.S. Pat. No. 7,827,562, and it is found that no results are obtained in15 of 100 negative samples. When the absorbing element is extruded,excessive liquid is absorbed by the test strip, to cause the flooding,so the compliance rate is only 85%. In the 50 samples that are confirmedof positive, positive results are obtained in only 35 samples, and theremaining samples (15 samples) are abandoned because the adjacent teststrips are overlapped and no accurate results are obtained, and thecompliance rate is only 70%.

Example 2—Detection Sensitivity Experiment

This embodiment is intended to illustrate the detection sensitivity ofthe apparatus and method in the present invention. Each sample solutionis detected with ten apparatuses, for a total of 300 tests. Salivasamples are used for detection for these apparatuses. The test stripsused have antigens of the detected drugs. The test strips use acompetition method, with antibodies labeled with colloidal gold in thelabeled area and antigen on the test line.

The apparatus is also detected by cocaine (COC), methylamphetamine(MAMP), phencyclidine (PCP), tetrahydrocannabinol (THC), morphine (MOP)or amphetamine (AMP) PBS solution, which contain 0, 0.5, 1.5 and 3 timesof the limit of detection. For example, the limit of detection of THC insaliva is 4 ng/ml. Therefore, the PBS solutions containing THC of 0ng/ml, 2 ng/ml, 6 ng/ml and 8 ng/ml are detected. The amount of thetested drugs is shown in the following table.

When detection is performed, the foregoing mentioned negative saliva,PBS, or spiked PBS are absorbed by the absorption sponge of the samplecollector, and then extruded into the absorption head and receivingchamber for testing. The liquid is allowed to enter the groove 206 tocontact the test strips by the capillary action. The test results arerecorded and shown in the table below 10 minutes later.

Drug (Limit of PBS + PBS + PBS + Detection) Saliva PBS 0.5× drug 1.5×drug 3× drug COC 0 ng/ml 0 ng/ml 10 ng/ml 30 ng/ml  60 ng/ml (20 ng/ml)MAMP 0 ng/ml 0 ng/ml 25 ng/ml 75 ng/ml 150 ng/ml (50 ng/ml) PCP 0 ng/ml0 ng/ml  5 ng/ml 15 ng/ml  30 ng/ml (10 ng/ml) THC 0 ng/ml 0 ng/ml  2ng/ml  6 ng/ml  12 ng/ml (4 ng/ml) MOP 0 ng/ml 0 ng/ml 20 ng/ml 60 ng/ml120 ng/ml (40 ng/ml) AMP 0 ng/ml 0 ng/ml 25 ng/ml 75 ng/ml 150 ng/ml (50ng/ml)The above results show that the prevent invention can obtain a goodsensitivity.

The invention shown and described herein may be implemented in theabsence of any elements, limitations specifically disclosed herein. Theterms and expressions used herein are for illustration rather thanlimitation, which do not exclude any equivalents of the features andportions described herein in the use of these terms and expressions, inaddition, it should be understood that various modifications arefeasible within the scope of the present invention. It is therefore tobe understood that, although the invention has been particularlydisclosed by various embodiments and alternative features, modificationsand variations of the concepts described herein may be employed by thoseof skilled in the art, and such modifications and variations will fallinto the scope of protection of the present invention as defined by theappended claims.

The contents of the articles, patents, patent applications, and allother documents and electronic information available or documentedherein are incorporated herein by reference in their entirety, as ifeach individual publication is specifically and individually indicatedfor reference. The applicant reserves the right to incorporate any andall materials and information from any such article, patent, patentapplication or other document into this application.

The invention claimed is:
 1. An apparatus for collecting and detectingan analyte in a fluid sample, comprising: a fluid sample collectionelement comprising: an absorbing element; one or more flexiblesheet-like structures, wherein through the engagement of said one ormore flexible sheet-like structures with an inner wall of a chamber, asealing of the chamber by said one or more flexible sheet-likestructures and the extrusion of the absorbing element is achieved, andwherein said one or more flexible sheet-like structures has an acutetriangle section that includes two long sides, one of the long sidesbeing perpendicular to an inner plug body and other long side beingsubstantially inclined with the inner plug body.
 2. The apparatusaccording to claim 1, wherein the absorbing element is extruded by aextrusion structure to release liquid samples during the engagement ofthe fluid sample collection element with the chamber.
 3. The apparatusaccording to claim 2, wherein the extrusion structure and a carrierstructure are an integrated structure or a one-shot injection moldedstructure.
 4. The apparatus according to claim 3, wherein the carriercomprises an inner surface and an outer surface, and the outer surfacehas one or more slots for accommodating a testing element.
 5. Theapparatus according to claim 4, wherein a testing element is disposed inthe slot, a sampling applying area of the testing element extendsoutwardly from the opening of the slot, so that a part of the samplingapplying area is located at the bottom of the chamber.
 6. The apparatusaccording to claim 3, wherein the carrier comprises a support structureand the support structure forms a space, and the extrusion structure islocated in the space.
 7. The apparatus according to claim 6, wherein theextrusion structure comprises an extrusion chamber, and one or morethrough-holes are provided at the bottom of the extrusion chamber, aliquid sample extruded from the absorbing element flow to the bottom ofthe chamber through the through-holes.
 8. The apparatus according toclaim 7, wherein the through-holes are included in the junction of theextrusion chamber with the inner surface of the carrier, and a liquidsample extruded from the absorbing element flow to the bottom of thechamber via the through-holes.
 9. The apparatus according to claim 1,wherein the flexible sheet-like structure is located on the inner plugbody.
 10. The apparatus according to claim 1, wherein the long sidebeing perpendicular to the inner plug is located above the long sideinclined with the inner plug body.
 11. The apparatus according to claim1, wherein the outer diameter formed by the flexible sheet-likestructure is greater than the inner diameter of the inner wall of thechamber.
 12. The apparatus according to claim 1, wherein a protrusionarea is provided in the chamber, and the protrusion area and the innerwall of the chamber form a liquid collection area.
 13. The apparatusaccording to claim 12, wherein a part of the sample applying area islocated at the collection area to contact with the liquid samples in thecollection area.
 14. An apparatus for collecting and detecting ananalyte in a fluid sample, comprising: a fluid sample collection elementcomprising: an absorbing element that absorbs fluid samples; a grippingportion that has an inner plug body, the inner plug body comprising aflexible sealing sheet-likes structure; and a connecting rod thatconnects the absorbing element and the gripping portion; a chamber foraccommodating a carrier therein, which has an opening and inner wall,wherein the flexible sealing sheet-like structure cooperates with theinner wall of the chamber, thereby forming an opening for sealing thechamber, and allowing the fluid sample collection element to be retainedin the chamber, and wherein the flexible sealing sheet-like structurehas an acute triangle section, the acute triangle including two longsides, wherein one of the long sides is perpendicular to the inner plugbody, and another of the long sides is substantially inclined with theinner plug body, wherein the long side that is perpendicular to theinner plug body is located above the other long side that is inclinedwith the inner plug body.
 15. The apparatus according to claim 14,wherein the inner plug is connected to the gripping portion.